Cancer has become one of the leading causes of death in the world's population. According to statistics, six people die every minute from cancer in China. Among them, lung cancer is a malignant disease with the No. 1 morbidity and mortality worldwide and throughout China. At present, surgical resection and conventional chemotherapy are commonly used in clinical practice, but the high recurrence rate and side effects of surgery and chemotherapy have always been clinical problems to be solved. It is urgent to employ new methods and means to treat patients with lung cancer and extend the lifetime of the patients. An aptamer is a single-stranded oligonucleotide sequence (ssDNA, RNA or modified RNA) that can be folded into a specific three-dimensional structure and specifically bound to a target by a spatial configuration. Since aptamers have the specificity to bind their targets, some of the aptamers can also inhibit the function of the target substance and block the signaling pathway in the cell by binding to the target, and thus, have the value to further develop a nucleic acid drug for specifically inhibiting the target.
Epirubicin (EPI) is a broad-spectrum chemotherapeutic drug used in the treatment of a variety of cancers (such as acute leukemia, malignant lymphoma, breast cancer, bronchial lung cancer, ovarian cancer, lung cancer, bladder cancer, stomach cancer, liver cancer and other solid tumors). Its mechanism of action is to directly intercalate into DNA base pairs, interfere with the transcription process, prevent the formation of mRNA, and thus inhibit the synthesis of DNA and RNA. It is a cell cycle non-specific drug and is effective for a variety of transplanted tumors. However, epirubicin is not specific for cell toxicity, and it can cause damage to other organs while killing tumor cells, affecting patient tolerance and therapeutic effects. Therefore, it is of great significance to develop a targeted drug that can carry cytotoxic drugs such as epirubicin, and perform targeted killing on tumors and reduce damage to other cells.
The aptamer is a short single-stranded DNA or RNA molecule with recognition activity evolved from systematic evolution of ligands by exponential enrichment (SELEX), which is a manual screening technique simulating the natural evolution process. It can be folded into a specific three-dimensional structure to bind to the target, and has the characteristics of high affinity, high specificity, no immunogenicity, easy synthesis, in vitro modification, good stability and the like. Some of the aptamers not only can bind to the target substance, but also can inhibit the function of target molecules, and show broad application prospects in the targeted treatment of diseases. Up to now, FDA has approved a nucleic acid aptamer specific for VEGF developed by Eyetch/Pfizer, pegaptanib sodium (trade name Macugen), for the treatment of age-related macular degeneration. In addition, in the field of tumor therapy, aptamers targeting VEGF, E2F, nucleolin and the like have also entered clinical research pipelines, revealing the prospect of nucleic acid aptamers in tumor therapy.
Although the SELEX technique has been applied to screening nucleic acid aptamers, the development and screening of aptamers that are truly useful remain very difficult in the art, and there are still very few aptamers that currently have binding ability or inhibitory effects on specific cancers.